We have established a functional E-neoantigen (Eneo) radioimmunoassay (RIA) which determines normal and pathological plasma levels of fibrinogen-fibrin degradation products in the presence of circulating fibrinogen (Fg). This RIA measures Eneo immunoreactivities of fragments X, Y and E engendered by the plasmin cleavage of Fg and fibrin (Fb). Immunochemically it could not discriminate between Fg-E and Fb-E, but it gave a parallel relationship between the inhibition curves of test plasmas and Fg-E standard in competition against the antigen-antibody reaction of 125I-Fg-E and Fg-absorbed anti-Fg-E serum. The assay was also validated by the fact that Fg-E added to test plasma could be recovered quantitatively. Eneo immunoreactivities were determined in the plasma of normal individuals and cancer patients. Normal values ranged from 3-20 ng/ml; most neoplasms were normal - 200 ng/ml - with the exception of two patients, one with promyelocytic leukemia complicated by disseminated intravascular coagulation who had 2027 ng/ml and the second had esophageal carcinoma followed by deep vein thrombosis who had 754 ng/ml. Other coagulation data collected from the patients were: Fibrinogen concentration, platelet count, antithrombin III level and thrombin time. Eneo values appeared to reflect best the altered hemostasis in malignancy.